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Thursday, October 8, 2020

Buddhism and psychology

From Wikipedia, the free encyclopedia
 
Buddhist monk Barry Kerzin participating in neuropsychology meditation research with EEG.

Buddhism includes an analysis of human psychology, emotion, cognition, behavior and motivation along with therapeutic practices. Buddhist psychology is embedded within the greater Buddhist ethical and philosophical system, and its psychological terminology is colored by ethical overtones. Buddhist psychology has two therapeutic goals: the healthy and virtuous life of a householder (samacariya, "harmonious living") and the ultimate goal of nirvana, the total cessation of dissatisfaction and suffering (dukkha).

Buddhism and the modern discipline of Psychology have multiple parallels and points of overlap. This includes a descriptive phenomenology of mental states, emotions and behaviors as well as theories of perception and unconscious mental factors. Psychotherapists such as Erich Fromm have found in Buddhist enlightenment experiences (e.g. kensho) the potential for transformation, healing and finding existential meaning. Some contemporary mental-health practitioners such as Jon Kabat-Zinn find ancient Buddhist practices (such as the development of mindfulness) of empirically therapeutic value, while Buddhist teachers such as Jack Kornfield see Western psychology as providing complementary practices for Buddhists.

Interaction

The establishment of Buddhism predates the field of psychology by over two millennia; thus, any assessment of Buddhism in terms of psychology is necessarily a modern invention. One of the first such assessments occurred when British Indologists started translating Buddhist texts from Pali and Sanskrit. The modern growth of Buddhism in the West and particularly the development of Buddhist modernism worldwide has led to the comparing and contrasting of European psychology and psychiatry with Buddhist theory and practice. According to Austrian psychologist Gerald Virtbauer, the contact of Buddhism and European Psychology has generally followed three main approaches:

  1. The presentation and exploration of parts of Buddhist teachings as a Psychology and psychological method for analyzing and modifying human experience.
  2. The integration of parts of the Buddhist teachings in already existing psychological or psychotherapeutic lines of thought (such as in Mindfulness-based cognitive therapy and in Acceptance and commitment therapy).
  3. Buddhist integration of Western psychological and social science knowledge into the Buddhist system (e.g., Buddhist modernism, Vipassana movement)

Psychology in the Tripitaka

The earliest Buddhist writings are preserved in three-part collections called Tipitaka (Pali; Skt. Tripitaka). The first part, the Sutta Pitaka contains a series of discourses attributed to the Buddha containing much psychological material.

A central feature of Buddhist psychology is its methodology which is based on personal experience through introspection and phenomenological self observation. According to the Buddha while initially unreliable, one's mind can be trained, calmed and cultivated so as to make introspection a refined and reliable method. This methodology is the foundation for the personal insight into the nature of the mind the Buddha is said to have achieved. While introspection is a key aspect of the Buddhist method; observation of a person's behavior is also important.

Perception and the self

Figure 1: The Pali Canon's Six Sextets:
 
  sense bases  
 
  f
e
e
l
i
n
g
   
 
  c
r
a
v
i
n
g
   
  "internal"
sense
organs
<–> "external"
sense
objects
 
 
contact
   
consciousness
 
 
 
  1. The six internal sense bases are the eye, ear,
    nose, tongue, body & mind.
  2. The six external sense bases are visible forms,
    sound, odor, flavors, touch & mental objects.
  3. Sense-specific consciousness arises dependent
    on an internal & an external sense base.
  4. Contact is the meeting of an internal sense
    base, external sense base & consciousness.
  5. Feeling is dependent on contact.
  6. Craving is dependent on feeling.
 Source: MN 148 (Thanissaro, 1998)    diagram details
 The Five Aggregates (pañca khandha)
according to the Pali Canon.
 
 
form (rūpa)
  4 elements
(mahābhūta)
 
 
   
    contact
(phassa)
    
 
consciousness
(viññāna)

 
 
 
 
 


 
 
 
  mental factors (cetasika)  
 
feeling
(vedanā)

 
 
 
perception
(sañña)

 
 
 
formation
(saṅkhāra)

 
 
 
 
 Source: MN 109 (Thanissaro, 2001)  |  diagram details

The early Buddhist texts outline a theory of perception and cognition based on the ayatanas (sense bases, sense media, sense spheres) which are categorized into sense organs, sense objects and awareness. The contact between these bases leads to a perceptual event as explained in Buddhist texts: "when the eye that is internal is intact and external visible forms come within its range and when there is an appropriate act of attention on the part of the mind, there is the emergence of perceptual consciousness."

The usual process of sense cognition is entangled with what the Buddha terms "papañca" (conceptual proliferation), a distortion and elaboration in the cognitive process of the raw sensation or feeling (vedana). This process of confabulation feeds back into the perceptual process itself. Therefore, perception for the Buddhists is not just based on the senses but also on our desires, interests and concepts and hence it is in a way unrealistic and misleading. The goal of Buddhist practice is then to remove these distractions and gain knowledge of things as they are (yatha-bhuta ñānadassanam).

This psycho-physical process is further linked with psychological craving, manas (conceit) and ditthi (dogmas, views). One of the most problematic views according to the Buddha, is the notion of a permanent and solid Self or 'pure ego'. This is because in early Buddhist psychology, there is no fixed self (atta; Sanskrit atman) but the delusion of self and clinging to a self concept affects all one's behaviors and leads to suffering. For the Buddha there is nothing uniform or substantial about a person, only a constantly changing stream of events or processes categorized under five categories called skandhas (heaps, aggregates), which includes the stream of consciousness (Vijñāna-sotam). False belief and attachment to an abiding ego-entity is at the root of most negative emotions.

The psychologist Daniel Goleman states:

The notion of an "empty self" posits that there is no "CEO of the mind," but rather something like committees constantly vying for power. In this view, the "self" is not a stable, enduring entity in control, but rather a mirage of the mind—not actually real, but merely seemingly so. While that notion seems contrary to our own everyday experience, it actually describes the deconstruction of self that cognitive neuroscience finds as it dissects the mind (most famously, Marvin Minsky's "society of mind"). So the Buddhist model of the self may turn out to fit the data far better than the notions that have dominated Psychological thinking for the last century.

The Buddha saw the human mind as a psycho-physical complex, a dynamic continuum called namarupa. Nama refers to the non-physical elements and rupa to the physical components. According to Padmasiri de Silva, "The mental and physical constitutents form one complex, and there is a mutual dependency of the mind on the body and of the body on the mind."

Motivation and emotion

Buddha's theory of human motivation is based on certain key factors shared by all human beings and is primarily concerned with the nature of human dissatisfaction (dukkha) and how to dispel it. In the suttas, human beings are said to be motivated by craving (tanha, literally 'thirst') of three types:

  • Kama tanha - craving for sensory gratification, sex, novel stimuli, and pleasure.
  • Bhava tanha - craving for survival or continued existence, also includes hunger and sleep as well as desire for power, wealth and fame.
  • Vibhava tanha - craving for annihilation, non-existence, also associated with aggression and violence towards oneself and others

These three basic drives have been compared to the Freudian drive theory of libido, ego, and thanatos respectively (de Silva, 1973). The arousal of these three cravings is derived from pleasant or unpleasant feelings (vedana), reactions to sense impressions with positive or negative hedonic tone. Cravings condition clinging or obsession (upadana) to sense impressions, leading to a vicious cycle of further craving and striving, which is ultimately unsatisfactory and stressful.

The suttas also enumerate three "unwholesome roots" (akusala mulas) of suffering, negative emotions and behavior: raga (passion or lust); dosa (hatred or malice); and moha (delusion, or false belief).  These are opposed by three wholesome roots: liberality, kindness and wisdom.

Feeling or affective reaction (vedana) is also at the source of the emotions and it is categorized in various ways; as physical or mental, as pleasant, unpleasant or neutral; and as rooted in the different senses. The Buddha also makes a distinction between worldly and unworldly or spiritual feelings, seeing spiritual feelings as superior. Out of these basic immediate reactions as well as our situational context, conceptualization and personal history arise more complex emotions, such as fear, hatred, hope or despair. The Buddhist theory of emotions also highlights the ethical and spiritual importance of positive emotions such as compassion and friendliness as antidotes for negative emotions and as vehicles for self development.

According to Padmasiri de Silva, in the early Buddhist texts emotions can be divided into four groups: "those which obstruct the ideal of the virtuous life sought by the layman, emotions that interfere with the recluse seeking the path of perfection, emotions enhancing the layman's ideal of the virtuous life and emotions developed by the recluse seeking the path of perfection."

The Unconscious

The early Buddhist texts such as the Pali Canon present a theory about latent mental tendencies (Anusaya, "latent bias," "predisposition", "latent disposition") which are pre-conscious or non-conscious These habitual patterns are later termed "Vāsanā" (impression) by the later Yogacara Buddhists and were held to reside in an unconscious mental layer. The term "fetter" is also associated with the latent tendencies.

A later Theravada text, the Abhidhammattha-sangaha (11th-12th century) says: “The latent dispositions are defilements which ‘lie along with’ the mental process to which they belong, rising to the surface as obsessions whenever they meet with suitable conditions” (Abhs 7.9). The Theravada school also holds that there is a subconscious stream of awareness termed the Bhavanga.

Another set of unconscious mental factors responsible for influencing one's behavior include the asavas (Sanskrit asrava, "influx, canker, inflows"). These factors are said to "intoxicate" and "befuddle" the mind. The Buddha taught that one had to remove them from the mind through practice in order to reach liberation. The asavas are said to arise from different factors: sensuality, aggression, cruelty, body, and individuality are some of the factors given.

The Yogacara school of Mahayana Buddhism (starting from the 3rd to 5th century CE) extended these ideas into what has been called a Buddhist theory of the Unconscious mind. This concept was termed the ālaya-vijñāna (the foundation consciousness) which stores karmic seeds (bija) and undergoes rebirth. This theory was incorporated into a wider Yogacara theory of the Eight Consciousnesses and is also held in Tibetan Buddhism.

Self development and cognitive behavioral practices

Meditating Buddhist monk in Khao Luang.

According to Padmal de Silva "Buddhist strategies represent a therapeutic model which treats the person as his/her agent of change, rather than as the recipient of externally imposed interventions." Silva argues that the Buddha saw each person responsible for their own personal development and considers this as being similar to the humanistic approach to psychology. Humanistic psychotherapy places much emphasis on helping the client achieve self-actualization and personal growth (e.g. Maslow).

Since Buddhist practice also encompasses practical wisdom, spiritual virtues and morality, it cannot be seen exclusively as another form of psychotherapy. It is more accurate to see it as a way of life or a way of being (Dharma).

Personal development in Buddhism is based upon the noble eightfold path which integrates ethics, wisdom or understanding (pañña) and psychological practices such as meditation (bhavana, cultivation, development). Self-actualization in traditional Buddhism is based on the ideas of Nirvana and Buddhahood. The highest state a human can achieve (an Arahant or a Buddha) is seen as being completely free from any kind of dissatisfaction or suffering, all negative mental tendencies, roots and influxes have been eliminated and there are only positive emotions like compassion and loving-kindness present.

Buddhist meditation is of two main types: Samatha is meant to calm and relax the mind, as well as develop focus and concentration by training attention on a single object; Vipassana is a means to gain insight or understanding into the nature of the mental processes and their impermanent, stressful and self-less qualities through the application of continuous and stable mindfulness and comprehension (Sampajañña). Though the ultimate goal of these practices are nirvana, the Buddha stated that they also bring mundane benefits such as relaxation, good sleep and pain reduction.

Buddhist texts also contain mental strategies of thought modification which are similar to Cognitive behavioral therapy techniques. A comparison of these systems of cognitive behavioral modification has been discussed by professor William Mikulas and Padmal de Silva.

According to Padmal de Silva these similarities include: "fear reduction by graded exposure and reciprocal inhibition; using rewards for promoting desirable behavior; modelling for inducing behavioral change; the use of stimulus control to eliminate undesirable behavior; the use of aversion to eliminate undesirable behavior; training in social skills; self-monitoring; control of intrusive thoughts by distraction, switching/stopping, incompatible thoughts, and by prolonged exposure to them; intense, covert, focusing on the unpleasant aspects of a stimulus or the unpleasant consequences of a response, to reduce attachment to the former and eliminate the latter; graded approach to the development of positive feelings towards others: use of external cues in behavior control; use of response cost to aid elimination of undesirable behavior; use of family members for carrying out behavior change programs; and cognitive-behavioral methods--for example, for grief."

An important early text for these cognitive therapeutic methods is the Vitakkasanthana Sutta (MN 20) (The Removal of Distracting Thoughts) and its commentary, the Papancasudani. For removing negative or intrusive thoughts, the Buddha recommended five methods in this sutta:

  1. Focus on an opposite or incompatible thought or object.
  2. Ponder on the perils and disadvantages of the thought, its harmful consequences.
  3. Ignore the thought and distract yourself from it through some other activity.
  4. Reflect on the removal or stopping of the causes of the target thought.
  5. Make a forceful mental effort.

Another recommended technique is from the Satipatthana Sutta, which outlines the practice of mindfulness, which is not just a formal meditation, but a skill of attentive awareness and self monitoring. In developing mindfulness, one is advised to be aware of all thoughts and sensations that arise, even unwanted or unpleasant ones and continuously attend to such thoughts. Eventually, through habituation and exposure, the intensity and unpleasantness of such thoughts will disappear.[9] Buddhist texts also promote the training of positive emotions such as loving-kindness, compassion, empathetic joy and equanimity.

Abnormal Psychology

The Pali Canon records that the Buddha distinguished between two kinds of illness (rogo): physical illness (kāyiko rogo) and mental illness (cetasiko rogo). The Buddha attributed mental illness to the arising of mental defilements (Kleshas) which are ultimately based on the unwholesome roots (three poisons) of greed, hatred and confusion. From the perspective of the Buddha, mental illness is a matter of degree, and ultimately, everyone who is not an awakened being is in some sense mentally ill. As the Buddha in the Pali canon states: "those beings are hard to find in the world who can admit freedom from mental disease even for one moment, save only those in whom the asavas are destroyed." Another set of negative qualities outlined by the Buddha are the five hindrances, which are said to prevent proper mental cultivation, these are: sense desire, hostility, sloth-torpor, restlessness-worry and doubt.

According to Edwina Pio, Buddhist texts see mental illness as being mainly psychogenic in nature (rooted mainly in "environmental stress and inappropriate learning").

The Pali canon also describes Buddhist monks (epitomized by the monk Gagga) with symptoms of what would today be called mental illness. An act which is against the monk's code of discipline (Vinaya) committed by someone who was "ummatta" - "out of his mind" was said by the Buddha to be pardonable. This was termed the madmans leave (ummattakasammuti) The texts also assume that this 'madness' can be cured or recovered from, or is at least an impermanent phenomenon, after which, during confession, the monk is considered sane by the sangha once more.

There are also stories of lay folk who show abnormal behavior due to the loss of their loved ones. Other Buddhist sources such as the Milinda Panha echo the theory that madness is caused mainly by personal and environmental circumstances.

Other abnormal behaviors described by the early sources include Intellectual disability, epilepsy, alcoholism, and suicide. Buddhagosa posits that the cause of suicide is mental illness based on factors such as loss of personal relations and physical illness.

Abhidhamma psychology

The third part (or pitaka, literally "basket") of the Tripitaka is known as the Abhidhamma (Pali; Skt. Abhidharma). The Abhidhamma works are historically later than the two other collections of the Tipitaka (3rd century BCE and later) and focus on phenomenological psychology. The Buddhist Abhidhamma works analyze the mind into elementary factors of experience called dharmas (Pali: dhammas). Dhammas are phenomenal factors or "psycho-physical events" whose interrelations and connections make up all streams of human experience. There are four categories of dharmas in the Theravada Abhidhamma: Citta (awareness), Cetasika (mental factors), Rūpa (physical occurrences, material form) and Nibbāna (cessation). Abhidhamma texts are then an attempt to list all possible factors of experience and all possible relationships between them. Among the achievements of the Abhidhamma psychologists was the outlining of a theory of emotions, a theory of personality types, and a psychology of ethical behavior.

Ven. Bhikkhu Bodhi, president of the Buddhist Publication Society, has synopsized the Abhidhamma as follows:

The system that the Abhidhamma Pitaka articulates is simultaneously a philosophy, a psychology, and an ethics, all integrated into the framework of a program for liberation.... The Abhidhamma's attempt to comprehend the nature of reality, contrary to that of classical science in the West, does not proceed from the standpoint of a neutral observer looking outwards towards the external world. The primary concern of the Abhidhamma is to understand the nature of experience, and thus the reality on which it focuses is conscious reality.... For this reason the philosophical enterprise of the Abhidhamma shades off into a phenomenological psychology. To facilitate the understanding of experienced reality, the Abhidhamma embarks upon an elaborate analysis of the mind as it presents itself to introspective meditation. It classifies consciousness into a variety of types, specifies the factors and functions of each type, correlates them with their objects and physiological bases, and shows how the different types of consciousness link up with each other and with material phenomena to constitute the ongoing process of experience.

Buddhism and psychology

Buddhism and psychology overlap in theory and in practice. Since the beginning of the 20th century, four strands of interplay have evolved:

  • descriptive phenomenology: scholars have found in Buddhist teachings a detailed introspective phenomenological psychology (particularly in the Abhidhamma which outlines various traits, emotions and personality types).
  • psychotherapeutic meaning: humanistic psychotherapists have found in Buddhism's non-dualistic approach and enlightenment experiences (such as in Zen kensho) the potential for transformation, healing and finding existential meaning. This connection was explained by a modification of Piaget's theory of cognitive development introducing the process of initiation.
  • clinical utility: some contemporary mental-health practitioners increasingly find ancient Buddhist practices (such as the development of mindfulness) of empirically proven therapeutic value.
  • popular psychology and spirituality: psychology has been popularized, and has become blended with spirituality in some forms of modern spirituality. Buddhist notions form an important ingredient of this modern mix.

Psychology

Caroline A. F. Rhys Davids was one of the first modern Psychologist to conceptualize canonical Buddhist writings in terms of psychology.

The contact between Buddhism and Psychology began with the work of the Pali Text Society scholars, whose main work was translating the Buddhist Pali Canon. In 1900, Indologist Caroline A. F. Rhys Davids published through the Pali Text Society a translation of the Theravada Abhidhamma's first book, the Dhamma Sangani, and entitled the translation, "Buddhist Manual of Psychological Ethics". In the introduction to this seminal work, Rhys Davids praised the sophistication of the Buddhist psychological system based on "a complex continuum of subjective phenomena" (dhammas) and the relationships and laws of causation that bound them (Rhys Davids, 1900, pp. xvi-xvii.). Buddhism's psychological orientation is a theme Rhys Davids pursued for decades as evidenced by her further publications, Buddhist Psychology: An Inquiry into the Analysis and Theory of Mind in Pali Literature (1914) and The Birth of Indian Psychology and its Development in Buddhism (1936).

An important event in the interchange of East and West occurred when American psychologist William James invited the Sri Lankan Buddhist Anagarika Dharmapala to lecture in his classes at Harvard University in December 1903. After Dharmapala lectured on Buddhism, James remarked, “This is the psychology everybody will be studying 25 years from now.” Later scholars such as David Kalupahana (The principles of Buddhist psychology, 1987), Padmal de Silva (Buddhism and behaviour modification, 1984), Edwina Pio (Buddhist Psychology: A Modern Perspective, 1988) and Hubert Benoit (Zen and the Psychology of Transformation, 1990) wrote about and compared Buddhism and Psychology directly. Writers in the field of Transpersonal psychology (which deals with religious experience, altered states of consciousness and similar topics) such as Ken Wilber also integrated Buddhist thought and practice into their work.

The 1960s and '70s saw the rapid growth of Western Buddhism, especially in the United States. In the 1970s, psychotherapeutic techniques using “mindfulness” were developed such as Hakomi therapy by Ron Kurtz (1934–2011), possibly the first mindfulness based therapy. Jon Kabat-Zinn's Mindfulness-Based Stress Reduction (MBSR) was a very influential development, introducing the term into Western Cognitive behavioral therapy practice. Kabat-Zinn's students Zindel V. Segal, J. Mark G. Williams and John D. Teasdale later developed Mindfulness-based cognitive therapy (MBCT) in 1987. In the early 2000s Vidyamala Burch and her organization Breathworks developed Mindfulness-Based Pain Management (MBPM).

Research by Sarah Lazar et al (2005) found brain areas that are thicker in practitioners of Insight meditation than control subjects who do not meditate.

More recent work has focused on clinical research of particular practices derived from Buddhism such as mindfulness meditation and compassion development (ex. the work of Jon Kabat-Zinn, Daniel Goleman) and on psycho-therapeutic practices which integrate meditative practices derived from Buddhism. From the perspective of Buddhism, various modern Buddhist teachers such as Jack Kornfield and Tara Brach have academic degrees in psychology.

Applying the tools of modern Neuropsychology (EEG, fMRI) to study Buddhist meditation is also an area of integration. One of the first figures in this area was neurologist James H. Austin, who wrote Zen and the Brain (1998). Others who have studied and written about this type of research include Richard Davidson, Alan Wallace, Rick Hanson (Buddha's Brain, 2009) and Zoran Josipovic. A recent review of the literature on the Neural mechanisms of mindfulness meditation concludes that the practice "exerts beneficial effects on physical and mental health, and cognitive performance" but that "the underlying neural mechanisms remain unclear." 

Japanese Psychology

Dr. Shoma Morita (1874-1938)

In Japan, a different strand of comparative thought developed, beginning with the publication, "Psychology of Zen Sect" (1893) and "Buddhist psychology" (1897), by Inoue Enryō (1858–1919). In 1920, Tomosada Iritani (1887–1957) administered a questionnaire to 43 persons dealing with Zen practice, in what was probably the first empirical psychological study of Zen. In the field of psychotherapy, Morita therapy was developed by Shoma Morita (1874-1938) who was influenced by Zen Buddhism.

Koji Sato (1905–1971) began the publication of the journal, Psychologia: An International Journal of Psychology in the Orient in 1957 with the aim of providing a comparative psychological dialogue between East and West (with contributions from Bruner, Fromm, and Jung). In the 1960s, Kasamatsu and Hirai used Electroencephalography to monitor the brains of Zen meditators. This led to the promotion of various studies covering psychiatry, physiology, and psychology of Zen by the Japanese ministry of education which were carried out in various laboratories. Another important researcher in this field, Prof. Yoshiharu Akishige, promoted Zen Psychology, the idea that the insights of Zen should not just be studied but that they should inform psychological practice. Research in this field continues with the work of Japanese psychologists such as Akira Onda and Osamu Ando.

In Japan, a popular psychotherapy based on Buddhism is Naikan therapy, developed from Jōdo Shinshū Buddhist introspection by Ishin Yoshimoto (1916–1988). Naikan therapy is used in correctional institutions, education, to treat alcohol dependence as well as by individuals seeking self development.

Buddhism and Psychoanalysis

Buddhism has some views which are comparable to Psychoanalytic theory. These include a view of the unconscious mind and unconscious thought processes, the view that unwholesome unconscious forces cause much of human suffering and the idea that one may gain insight into these thought processes through various practices, including what Freud called "evenly suspended attention." A variety of teachers, clinicians and writers such as D.T. Suzuki, Carl Jung, Erich Fromm, Alan Watts, Tara Brach, Jack Kornfield and Sharon Salzberg have attempted to bridge and integrate psycho-analysis and Buddhism. British barrister Christmas Humphreys has referred to mid-twentieth century collaborations between psychoanalysts and Buddhist scholars as a meeting between: "Two of the most powerful forces operating in the Western mind today."

D.T. Suzuki's influence

One of the most important influences on the spread of Buddhism in the west was Zen scholar D.T. Suzuki. He collaborated with psycho-analysts Carl Jung, Karen Horney and Erich Fromm.

Carl Jung wrote the foreword to Suzuki's Introduction to Zen Buddhism, first published together in 1948. In his foreword, Jung highlights the enlightenment experience of satori as the "unsurpassed transformation to wholeness" for Zen practitioners. And while acknowledging the inadequacy of Psychologist attempts to comprehend satori through the lens of intellectualism, Jung nonetheless contends that due to their shared goal of self transformation: "The only movement within our culture which partly has, and partly should have, some understanding of these aspirations [for such enlightenment] is psychotherapy."

Referencing Jung and Suzuki's collaboration as well as the efforts of others, humanistic philosopher and psychoanalyst Erich Fromm noted that: "There is an unmistakable and increasing interest in Zen Buddhism among psychoanalysts". One influential psychoanalyst who explored Zen was Karen Horney, who traveled to Japan in 1952 to meet with Suzuki and who advised her colleagues to listen to their clients with a "Zen-like concentration and non attachment".

Suzuki, Fromm and other psychoanalysts collaborated at a 1957 workshop on "Zen Buddhism and Psychoanalysis" in Cuernavaca, Mexico. Fromm contends that, at the turn of the twentieth century, most psychotherapeutic patients sought treatment due to medical-like symptoms that hindered their social functioning. However, by mid-century, the majority of psychoanalytic patients lacked overt symptoms and functioned well but instead suffered from an "inner deadness" and an "alienation from oneself". Paraphrasing Suzuki broadly, Fromm continues:

Zen is the art of seeing into the nature of one's being; it is a way from bondage to freedom; it liberates our natural energies; ... and it impels us to express our faculty for happiness and love. [...] [W]hat can be said with more certainty is that the knowledge of Zen, and a concern with it, can have a most fertile and clarifying influence on the theory and technique of psychoanalysis. Zen, different as it is in its method from psychoanalysis, can sharpen the focus, throw new light on the nature of insight, and heighten the sense of what it is to see, what it is to be creative, what it is to overcome the affective contaminations and false intellectualizations which are the necessary results of experience based on the subject-object split"

Buddhist psychoanalytic dialogue and integration

The dialogue between Buddhism and psychoanalysis has continued with the work of psychiatrists such as Mark Epstein, Nina Coltart, Jack Engler, Axel Hoffer, Jeremy D. Safran, David Brazier, and Jeffrey B. Rubin.

Nina Coltart (1927-1997) was the Director of the London Clinic of Psychoanalysis, a neo-Freudian and a Buddhist. She theorized that there are distinct similarities in the transformation of the self that occurs in both psychoanalysis and Buddhism. She believed that the practice of Buddhism and Psychoanalysis where "mutually reinforcing and clarifying" (Coltart, The practice of psychoanalysis and Buddhism).

Mark Epstein is an American psychiatrist who practiced Buddhism in Thailand under Ajahn Chah and has since written several books on psychoanalysis and Buddhism (Thoughts Without a Thinker 1995, Psychotherapy Without the Self, 2008). Epstein relates the Buddhist Four Noble Truths to primary narcissism as described by Donald Winnicott in his theory on the true self and false self. The first truth highlights the inevitability of humiliation in our lives of our narcissistic self-esteem. The second truth speaks of the primal thirst that makes such humiliation inevitable. The third truth promises release by developing a realistic self-image, and the fourth truth spells out the means of accomplishing that.

Jeffrey B. Rubin has also written on the integration of these two practices in Psychotherapy and Buddhism, Toward an Integration (1996). In this text, he criticizes the Buddhist idea of enlightenment as a total purification of mind: "From the psychoanalytic perspective, a static, conflict-free sphere-a psychological "safehouse" -beyond the vicissitudes of conflict and conditioning where mind is immune to various aspects of affective life such as self-interest, egocentricity, fear, lust, greed, and suffering is quixotic. Since conflict and suffering seem to be inevitable aspects of human life, the ideal of Enlightenment may be asymptotic, that is, an unreachable ideal." He points to scandals and abuses by American Buddhist teachers as examples. Rubin also outlines a case study of the psychoanalytic treatment of a Buddhist meditator and notes that meditation has been largely ignored and devalued by psychoanalysts. He argues that Buddhist meditation can provide an important contribution to the practice of psychoanalytic listening by improving an analyst's capacity for attention and recommends meditation for psychoanalysts.

Axel Hoffer has contributed to this area as editor of "Freud and the Buddha", which collects several essays by psychoanalysts and a Buddhist scholar, Andrew Olendzki. Olendzki outlines an important problematic between the two systems, the Freudian practice of free association, which from the Buddhist perspective is based on: “The reflexive tendency of the mind to incessantly make a narrative of everything that arises in experience is itself the cause of much of our suffering, and meditation offers a refreshing refuge from mapping every datum of sensory input to the macro-construction of a meaningful self.” Olendzki also argues that for the Buddhist, the psychoanalytic focus on linguistic narrativity distracts us from immediate experience.

David Brazier

David Brazier is a psychotherapist who combines psychotherapy and Buddhism (Zen therapy, 1995). Brazier points to various possible translations of the Pali terms of the Four Noble Truths, which give a new insight into these truths. The traditional translations of samudhaya and nirodha are "origin" and "cessation". Coupled with the translation of dukkha as "suffering", this gives rise to a causal explanation of suffering, and the impression that suffering can be totally terminated. The translation given by David Brazier gives a different interpretation to the Four Noble Truths.

  1. Dukkha: existence is imperfect, it's like a wheel that's not straight into the axis;
  2. Samudhaya: simultaneously with the experience of dukkha there arises tanha, thirst: the dissatisfaction with what is and the yearning that life should be different from what it is. We keep imprisoned in this yearning when we don't see reality as it is, namely imperfect and ever-changing;
  3. Nirodha: we can confine this yearning (that reality is different from what it is), and perceive reality as it is, whereby our suffering from the imperfectness becomes confined;
  4. Marga: this confinement is possible by following the Eightfold Path.

In this translation, samudhaya means that the uneasiness that's inherent to life arises together with the craving that life's event would be different. The translation of nirodha as confinement means that this craving is a natural reaction, which cannot be totally escaped or ceased, but can be limited, which gives us freedom.

Gestalt therapy

Gestalt Therapy, an approach created by Fritz Perls, was based on phenomenology, existentialism and also Zen Buddhism and Taoism. Perls spent some time in Japanese Zen monasteries and his therapeutic techniques include mindfulness practices and focusing on the present moment. Practices outlined by Perls himself in Ego, hunger and aggression (1969), such as “concentration on eating” (“we have to be fully aware of the fact that we are eating”) and “awareness continuum” are strikingly similar to Buddhist mindfulness training. Other authors in Gestalt Therapy who were influenced by Buddhism are Barry Stevens (therapist) and Dick Price (who developed Gestalt Practice by including Buddhist meditation).

According to Crocker, an important Buddhist element of Gestalt is that a “person is simply allowing what-is in the present moment to reveal itself to him and out of that receptivity is responding with ‘no-mind’”.

More recently, Claudio Naranjo has written about the practice of Gestalt and Tibetan Buddhism.

Existential and Humanistic psychology

Both existential and humanistic models of human psychology stress the importance of personal responsibility and freedom of choice, ideas which are central to Buddhist ethics and psychology.

Humanistic psychology's focus on developing the ‘fully functioning person’ (Carl Rogers) and self actualization (Maslow) is similar to the Buddhist attitude of self development as an ultimate human end. The idea of person-centered therapy can also be compared to the Buddhist view that the individual is ultimately responsible for their own development, that a Buddhist teacher is just a guide and that the patient can be “a light unto themselves”.

Carl Rogers's idea of "unconditional positive regard" and his stress on the importance of empathy has been compared to Buddhist conceptions of compassion (Karuṇā).

Mindfulness meditation has been seen as a way to aid the practice of person centered psychotherapy. Person centered therapist Manu Buzzano has written that "It seemed clear that regular meditation practice did help me in offering congruence, empathy and unconditional positive regard." He subsequently interviewed other person centered therapists who practiced meditation and found that it enhanced their empathy, nonjudgmental openness and quality of the relationship with their clients.

A comparison has also been made between Marshall Rosenberg's Nonviolent Communication and Buddhist ideals of right speech, both in theory and in manifesting Buddhist ideals in practice.

Padmasiri de Silva sees the focus of existential psychology on the "tragic sense of life" just a different expression of the Buddhist concept of dukkha. The existential concept of anxiety or angst as a response to the human condition also resonates with the Buddhist analysis of fear and despair. The Buddhist monk Nanavira Thera in the preface to his "Notes on Dhamma" wrote that the work of the existential philosophers offered a way to approach the Buddhist texts, as they ask the type of questions about feelings of anxiety and the nature of existence with which the Buddha begins his analysis. Nanavira also states that those who have understood the Buddha's message have gone beyond the existentialists and no longer see their questions as valid. Edward Conze likewise sees the parallel between the Buddhists and Existentialists only preliminary: "In terms of the Four Truths, the existentialists have only the first, which teaches that everything is ill. Of the second, which assigns the origin of ill to craving, they have only a very imperfect grasp. As for the third and fourth, they are quite unheard of...Knowing no way out, they are manufacturers of their own woes."

Positive Psychology

The growing field of Positive psychology shares with Buddhism a focus on developing a positive emotions and personal strengths and virtues with the goal of improving human well-being. Positive psychology also describes the futility of the "hedonic treadmill", the chasing of ephemeral pleasures and gains in search of lasting happiness. Buddhism holds that this very same striving is at the very root of human unhappiness.

The Buddhist concept and practice of mindfulness meditation has been adopted by psychologists such as Rick Hanson (Buddha's brain, 2009), T.B. Kashdan & J. Ciarrochi (Mindfulness, acceptance, and positive psychology, 2013) and Itai Ivtzan (Mindfulness in Positive Psychology, 2016). Kirk W. Brown and Richard M. Ryan of the University of Pennsylvania have developed a 15-item "Mindful attention awareness scale" to measure dispositional mindfulness.

The concept of Flow studied by Mihaly Csikszentmihalyi has been compared to Buddhist meditative states such as samadhi and mindfulness. Ronald Siegel describes flow as “mindfulness while accomplishing something.” Nobo Komagata and Sachiko Komagata, however, are critical of characterizing the notion of “flow” as a special case of mindfulness, noting that the connection is more complicated. Zen Buddhism has a concept called Mushin (無心, no mind) which is also similar to flow.

Christopher K. Germer, clinical instructor in psychology at Harvard Medical School and a founding member of the Institute for Meditation and Psychotherapy, has stated: "Positive psychology, which focuses on human flourishing rather than mental illness, is also learning a lot from Buddhism, particularly how mindfulness and compassion can enhance wellbeing. This has been the domain of Buddhism for the past two millennia and we’re just adding a scientific perspective."

Martin Seligman and Buddhist monk Thanissaro Bhikkhu have pointed out that the framework of Positive psychology is ethically neutral, and hence within that framework, you could argue that "a serial killer leads a pleasant life, a skilled Mafia hit man leads a good life, and a fanatical terrorist leads a meaningful life." Thanissaro argues that Positive psychology should also look into the ethical dimensions of the good life. Regarding the example of flow states he writes:

A common assumption is that what you do to induce a sense of flow is purely a personal issue, and ultimately what you do doesn’t really matter. What matters is the fact of psychological flow. You’re most likely to experience flow wherever you have the skill, and you're most likely to develop skill wherever you have the aptitude, whether it’s in music, sport, hunting, meditating, etc. From the Buddha’s point of view, however, it really does matter what you do to gain gratification, for some skills are more conducive to stable, long-term happiness than others, due to their long-term consequences.

The skills that Thanissaro argues are more conductive to happiness include Buddhist virtues like harmlessness, generosity, moral restraint, and the development of good will as well as mindfulness, concentration, discernment.

Naropa University

"Buddhism will come to the West as a psychology."

- Chogyam Trungpa, 1974

In his introduction to his 1975 book, Glimpses of the Abhidharma, Chogyam Trungpa Rinpoche wrote:

Many modern psychologists have found that the discoveries and explanations of the abhidharma coincide with their own recent discoveries and new ideas; as though the Abhidharma, which was taught 2,500 years ago, had been redeveloped in the modern idiom.

Trungpa Rinpoche's book goes on to describe the nanosecond phenomenological sequence by which a sensation becomes conscious using the Buddhist concepts of the "five aggregates."

In 1974, Trungpa Rinpoche founded the Naropa Institute, now called Naropa University. Since 1975, this accredited university has offered degrees in "contemplative psychology."

Mind and life institute

Every two years, since 1987, the Dalai Lama has convened "Mind and Life" gatherings of Buddhists and scientists. Reflecting on one Mind and Life session in March 2000, psychologist Daniel Goleman notes:

Since the time of Gautama Buddha in the fifth century BC, an analysis of the mind and its workings has been central to the practices of his followers. This analysis was codified during the first millennium after his death within the system called, in the Pali language of Buddha's day, Abhidhamma (or Abhidharma in Sanskrit), which means 'ultimate doctrine'.... Every branch of Buddhism today has a version of these basic psychological teachings on the mind, as well as its own refinements.

Buddhist techniques in clinical settings

For over a millennium, throughout the world, Buddhist practices have been used for non-Buddhist ends. More recently, clinical psychologists, theorists and researchers have incorporated Buddhist practices in widespread formalized psychotherapies. Buddhist mindfulness practices have been explicitly incorporated into a variety of psychological treatments. More tangentially, psychotherapies dealing with cognitive restructuring share core principles with ancient Buddhist antidotes to personal suffering.

Mindfulness practices

Fromm  distinguishes between two types of meditative techniques that have been used in psychotherapy:

  1. auto-suggestion used to induce relaxation;
  2. meditation "to achieve a higher degree of non-attachment, of non-greed, and of non-illusion; briefly, those that serve to reach a higher level of being" (p. 50).

Fromm attributes techniques associated with the latter to Buddhist mindfulness practices.

Two increasingly popular therapeutic practices using Buddhist mindfulness techniques are Jon Kabat-Zinn's Mindfulness-Based Stress Reduction (MBSR) and Marsha M. Linehan's Dialectical Behavioral Therapy (DBT). Other prominent therapies that use mindfulness include Steven C. Hayes' Acceptance and Commitment Therapy (ACT), Adaptation Practice founded in 1978 by the British psychiatrist and Zen Buddhist Clive Sherlock and, based on MBSR, Mindfulness-based Cognitive Therapy (MBCT) (Segal et al., 2002).

Clinical researchers have found Buddhist mindfulness practices to help alleviate anxiety, depression and certain personality disorders.

Mindfulness Based Stress Reduction (MBSR)

Kabat-Zinn developed the eight-week MBSR program over a ten-year period with over four thousand patients at the University of Massachusetts Medical Center. Describing the MBSR program, Kabat-Zinn writes:

This 'work' involves above all the regular, disciplined practice of moment-to-moment awareness or mindfulness, the complete 'owning' of each moment of your experience, good, bad, or ugly. This is the essence of full catastrophe living.

According to Kabat-Zinn, a one-time Zen practitioner,

Although at this time mindfulness meditation is most commonly taught and practiced within the context of Buddhism, its essence is universal.... Yet it is no accident that mindfulness comes out of Buddhism, which has as its overriding concerns the relief of suffering and the dispelling of illusions.

It would be based on relatively intensive training in Buddhist meditation without the Buddhism (as I liked to put it), and yoga.

Kabat-Zinn describes the MBSR program, as well as its scientific basis and the evidence for its clinical effectiveness, in his 1990 book Full Catastrophe Living, which was revised and reissued in 2013.

Mindfulness-based pain management

Mindfulness-based pain management (MBPM) is a mindfulness-based intervention (MBI) providing specific applications for people living with chronic pain and illness. Adapting the core concepts and practices of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), MBPM includes a distinctive emphasis on the practice of 'loving-kindness', and has been seen as sensitive to concerns about removing mindfulness teaching from its original ethical framework within Buddhism. It was developed by Vidyamala Burch and is delivered through the programs of Breathworks. It has been subject to a range of clinical studies demonstrating its effectiveness.

Dialectical Behavioral Therapy (DBT)

In writing about DBT, Zen practitioner Linehan  states:

As its name suggests, its overriding characteristic is an emphasis on 'dialectics' – that is, the reconciliation of opposites in a continual process of synthesis.... This emphasis on acceptance as a balance to change flows directly from the integration of a perspective drawn from Eastern (Zen) practice with Western psychological practice.

Similarly, Linehan  writes:

Mindfulness skills are central to DBT.... They are the first skills taught and are [reviewed] ... every week.... The skills are psychological and behavioral versions of meditation practices from Eastern spiritual training. I have drawn most heavily from the practice of Zen

Controlled clinical studies have demonstrated DBT's effectiveness for people with borderline personality disorder.

Acceptance and Commitment Therapy (ACT)

ACT did not explicitly emerge from Buddhism, but its concepts often parallel ideas from Buddhist and mystical traditions. ACT has been defined by its originators as a method that "uses acceptance and mindfulness processes, and commitment and behavioral activation processes to produce psychological flexibility.".

Mindfulness in ACT is defined to be a combination of four aspects of the psychological flexibility model, which is ACT's applied theory:

  1. Acceptance (openness to and engagement with present experience);
  2. Cognitive defusion (attending to the ongoing process of thought instead of automatically interacting with events as structured by prediction, judgment, and interpretation);
  3. Contact with the present moment (attention to the present external and internal world in a manner that is flexible, fluid, and voluntary);
  4. A transcendent sense of self or "self as context" (an interconnected sense of consciousness that maintains contact with the "I/Here/Nowness" of awareness and its interconnection with "You/There/Then").

These four aspects of mindfulness in ACT are argued to stem from Relational Frame Theory, the research program on language and cognition that underlies ACT at the basic level. For example, "self as context" is argued to emerge from deictic verbal relations such as I/You, or Here/There, which RFT laboratories have shown to help establish perspective taking skills and interconnection with others.

Most ACT self-help books (e.g.,) and many tested ACT protocols teach formal contemplative practice skills, but by this definition of mindfulness, such defusion skills as word repetition (taking a difficult thought, distilling it to a single word, and saying it repeatedly out loud for 30 seconds) are also viewed as mindfulness methods.

Adaptation Practice

The British psychiatrist Clive Sherlock, who trained in the traditional Rinzai School of Zen, developed Adaptation Practice (Ap), the foundation of mindfulness, in 1977 based on the profound mindfulness/awareness training of Zen daily-life practice and meditation. Adaptation Practice is used for long-term relief of depression, anxiety, anger, stress and other emotional problems.

Cognitive restructuring

Dr. Albert Ellis, considered the "grandfather of cognitive-behavioral therapy" (CBT), has written:

Many of the principles incorporated in the theory of rational-emotive psychotherapy are not new; some of them, in fact, were originally stated several thousands of years ago, especially by the Greek and Roman Stoic philosophers (such as Epictetus and Marcus Aurelius) and by some of the ancient Taoist and Buddhist thinkers (see Suzuki, 1956, and Watts, 1959, 1960).

To give but one example, Buddhism identifies anger and ill-will as basic hindrances to spiritual development (see, for instance, the Five Hindrances, Ten Fetters and kilesas). A common Buddhist antidote for anger is the use of active contemplation of loving thoughts (see, for instance, metta). This is similar to using a CBT technique known as "emotional training" which Ellis  describes in the following manner:

Think of an intensely pleasant experience you have had with the person with whom you now feel angry. When you have fantasized such a pleasant experience and have actually given yourself unusually good, intensely warm feelings toward that person as a result of this remembrance, continue the process. Recall pleasant experiences and good feelings, and try to make these feelings paramount over your feelings of hostility.

Reaction from Buddhist traditionalists

Some traditional Buddhist practitioners have expressed concern that attempts to view Buddhism through the lens of psychology diminishes the Buddha's liberating message.

Patrick Kearney has written that the effort to integrate the teachings of the Buddha by interpreting it through the view of psychologies has led to "a growing confusion about the nature of Buddhist teachings and a willingness to distort and dilute these teachings". He is critical of Jack Kornfield and Mark Epstein for holding that psychological techniques are a necessity for some Buddhists and of Jeffrey Rubin for writing that enlightenment might not be possible. Kearney writes:

Epstein and Rubin want to rewrite Buddhism on their own terms, taking the ocean of the Buddha’s wisdom and reducing it to a puddle small enough to accommodate the views of Freud and his successors.


Romantic /
humanistic
psychology
early
Buddhism
spiritual
illness
divided self clinging
ultimate
experience
feeling of
oneness
knowledge of
Awakening
cure on-going
personal
integration
Awakening

American Theravada monk Thanissaro Bhikkhu has also criticized the interpretation of Buddhism through Psychology, which has different values and goals, derived from roots such as European Romanticism and Protestant Christianity. He also identifies broad commonalities between "Romantic/humanistic psychology" and early Buddhism: beliefs in human (versus divine) intervention with an approach that is experiential, pragmatic and therapeutic. Thanissaro Bhikkhu traces the roots of modern spiritual ideals from German Romantic Era philosopher Immanuel Kant through American psychologist and philosopher William James, Jung and humanistic psychologist Abraham Maslow. Thanissaro sees their view as centered on the idea of healing the 'divided self', an idea which is alien to Buddhism. Thanissaro asserts that there are also core differences between Romantic/humanistic psychology and Buddhism. These are summarized in the adjacent table. Thanissaro implicitly deems those who impose Romantic/humanistic goals on the Buddha's message as "Buddhist Romantics."

The same similarities have been recognized by David McMahan when describing Buddhist modernism.

Recognizing the widespread alienation and social fragmentation of modern life, Thanissaro Bhikkhu writes:

When Buddhist Romanticism speaks to these needs, it opens the gate to areas of dharma [the Buddha's teachings] that can help many people find the solace they’re looking for. In doing so, it augments the work of psychotherapy [...] However, Buddhist Romanticism also helps close the gate to areas of the dharma that would challenge people in their hope for an ultimate happiness based on interconnectedness. Traditional dharma calls for renunciation and sacrifice, on the grounds that all interconnectedness is essentially unstable, and any happiness based on this instability is an invitation to suffering. True happiness has to go beyond interdependence and interconnectedness to the unconditioned [...] [T]he gate [of Buddhist Romanticism] closes off radical areas of the dharma designed to address levels of suffering remaining even when a sense of wholeness has been mastered."

Another Theravada monk, Bhikkhu Bodhi has also criticized the presentation of certain Buddhist teachings mixed with psychological and Humanistic views as being authentic Buddhism. This risks losing the essence of the liberating and radical message of the Buddha, which is focused on attaining nirvana:

What I am concerned about is the trend, common among present-day Buddhist teachers, of recasting the core principles of the Buddha's teachings into largely psychological terms and then saying, "This is Dhamma." When this is done we may never get to see that the real purpose of the teaching, in its own framework, is not to induce "healing" or "wholeness" or "self-acceptance," but to propel the mind in the direction of deliverance – and to do so by attenuating, and finally extricating, all those mental factors responsible for our bondage and suffering. We should remember that the Buddha did not teach the Dhamma as an "art of living" – though it includes that – but above all as a path to deliverance, a path to final liberation and enlightenment. And what the Buddha means by enlightenment is not a celebration of the limitations of the human condition, not a passive submission to our frailties, but an overcoming of those limitations by making a radical, revolutionary breakthrough to an altogether different dimension of being.

Popular psychology and spirituality

Mainstream teachers and popularizers

In 1961, philosopher and professor Alan Watts wrote:

If we look deeply into such ways of life as Buddhism and Taoism, Vedanta and Yoga, we do not find either philosophy or religion as these are understood in the West. We find something more nearly resembling psychotherapy.... The main resemblance between these Eastern ways of life and Psychotherapy is in the concern of both with bringing about changes of consciousness, changes in our ways of feeling our own existence and our relation to human society and the natural world. The psychotherapist has, for the most part, been interested in changing the consciousness of peculiarly disturbed individuals. The disciplines of Buddhism and Taoism are, however, concerned with changing the consciousness of normal, socially adjusted people.

Since Watts's early observations and musings, there have been many other important contributors to the contemporary popularization of the integration of Buddhist meditation with psychology including Kornfield (1993), Joseph Goldstein, Tara Brach, Epstein (1995) and Nhat Hanh (1998).

Education and research

Researchers interested in studying the intersection of Buddhism and psychology in North America have had to either fit themselves into Eastern Studies programs, psychology programs or engage in a program of private study. North American programs at accredited institutions dedicated to Buddhism and psychology are few. There is a minor (soon to be major) program at the University of Toronto called Buddhism and Mental Health.

As for clinical training, there is an accredited Master's program in Contemplative Psychotherapy offered at Naropa University in Boulder, CO. The curriculum is a hybrid of Buddhist psychology and psychotherapeutic approaches, and incorporates several group retreats and ongoing meditation practice. The program, which was founded in 1978, is designed to prepare for licensure as a professional counselor.

Physical object

From Wikipedia, the free encyclopedia

A bubble of exhaled gas in water

In common usage, a physical object or physical body (or simply an object or body) is a collection of matter within a defined contiguous boundary in three-dimensional space. The boundary must be defined and identified by the properties of the material. The boundary may change over time. The boundary is usually the visible or tangible surface of the object. The matter in the object is constrained (to a greater or lesser degree) to move as one object. The boundary may move in space relative to other objects that it is not attached to (through translation and rotation). An object's boundary may also deform and change over time in other ways.

Also in common usage, an object is not constrained to consist of the same collection of matter. Atoms or parts of an object may change over time. An object is defined by the simplest representation of the boundary consistent with the observations. However the laws of Physics only apply directly to objects that consist of the same collection of matter.

In physics, an object is an identifiable collection of matter, which may be constrained by an identifiable boundary, and may move as a unit by translation or rotation, in 3-dimensional space.

Each object has a unique identity, independent of any other properties. Two objects may be identical, in all properties except position, but still remain distinguishable. In most cases the boundaries of two objects may not overlap at any point in time. The property of identity allows objects to be counted.

Examples of models of physical bodies include, but are not limited to a particle, several interacting smaller bodies (particles or other), and continuous media.

The common conception of physical objects includes that they have extension in the physical world, although there do exist theories of quantum physics and cosmology which may challenge this. In modern physics, "extension" is understood in terms of the spacetime: roughly speaking, it means that for a given moment of time the body has some location in the space, although not necessarily a point. A physical body as a whole is assumed to have such quantitative properties as mass, momentum, electric charge, other conserving quantities, and possibly other quantities.

An object with known composition and described in an adequate physical theory is an example of physical system.

In common usage

An object is known by the application of senses. The properties of an object are inferred by learning and reasoning based on the information perceived. Abstractly, an object is a construction of our mind consistent with the information provided by our senses, using Occam's razor.

In common usage an object is the material inside the boundary of an object, in 3-dimensional space. The boundary of an object is a contiguous surface which may be used to determine what is inside, and what is outside an object. An object is a single piece of material, whose extent is determined by a description based on the properties of the material. An imaginary sphere of granite within a larger block of granite would not be considered an identifiable object, in common usage. A fossilized skull encased in a rock may be considered an object because it is possible to determine the extent of the skull based on the properties of the material.

For a rigid body, the boundary of an object may change over time by continuous translation and rotation. For a deformable body the boundary may also be continuously deformed over time in other ways.

An object has an identity. In general two objects with identical properties, other than position at an instance in time, may be distinguished as two objects and may not occupy the same space at the same time (excluding component objects). An object's identity may be tracked using the continuity of the change in its boundary over time. The identity of objects allows objects to be arranged in sets and counted.

The material in an object may change over time. For example, a rock may wear away or have pieces broken off it. The object will be regarded as the same object after the addition or removal of material, if the system may be more simply described with the continued existence of the object, than in any other way. The addition or removal of material may discontinuously change the boundary of the object. The continuation of the objects identity is then based on the description of the system by continued identify being simpler than without continued identity.

For example, a particular car might have all its wheels changed, and still be regarded as the same car.

The identity of an object may not split. If an object is broken into two pieces at most one of the pieces has the same identity. An object's identity may also be destroyed if the simplest description of the system at a point in time changes from identifying the object to not identifying it. Also an object's identity is created at the first point in time that the simplest model of the system consistent with perception identifies it.

An object may be composed of components. A component is an object completely within the boundary of a containing object.

Classical mechanics

In classical mechanics a physical body is collection of matter having properties including mass, velocity, momentum and energy. The matter exists in a volume of three-dimensional space. This space is its extension.

Under Newtonian gravity the gravitational field further away than the furthest extent of an object is determined only by the mass and the position of the center of mass.

Interactions between objects are partly described by orientation and external shape.

In continuum mechanics an object may be described as a collection of sub objects, down to an infinitesimal division, which interact with each other by forces which may be described internally by pressure and mechanical stress.

Quantum mechanics

In quantum mechanics an object is a particle or collection of particles. Until measured, a particle does not have a physical position. A particle is defined by a probability distribution of finding the particle at a particular position. There is a limit to the accuracy with which the position and velocity may be measured. A particle or collection of particles is described by a quantum state.

These ideas vary from the common usage understanding of what an object is.

String theory

In particle physics, there is a debate as to whether some elementary particles are not bodies, but are points without extension in physical space within space-time, or are always extended in at least one dimension of space as in string theory or M theory.

In psychology

In some branches of psychology, depending on school of thought, a physical object has physical properties, as compared to mental objects. In (reductionistic) behaviorism, objects and their properties are the (only) meaningful objects of study. While in the modern day behavioral psychotherapy it is still only the means for goal oriented behavior modifications, in Body Psychotherapy it is not a means only anymore, but its felt sense is a goal of its own. In cognitive psychology, physical bodies as they occur in biology are studied in order to understand the mind, which may not be a physical body, as in functionalist schools of thought.

In philosophy

A physical body is an enduring object that exists throughout a particular trajectory of space and orientation over a particular duration of time, and which is located in the world of physical space (i.e., as studied by physics). This contrasts with abstract objects such as mathematical objects which do not exist at any particular time or place.

Examples are a cloud, a human body, a weight, a billiard ball, a table, or a proton. This is contrasted with abstract objects such as mental objects, which exist in the mental world, and mathematical objects. Other examples that are not physical bodies are emotions, the concept of "justice", a feeling of hatred, or the number "3". In some philosophies, like the idealism of George Berkeley, a physical body is a mental object, but still has extension in the space of a visual field.

Wednesday, October 7, 2020

DNA replication

From Wikipedia, the free encyclopedia
 
DNA replication: The double helix is un'zipped' and unwound, then each separated strand (turquoise) acts as a template for replicating a new partner strand (green). Nucleotides (bases) are matched to synthesize the new partner strands into two new double helices.

In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance. The cell possesses the distinctive property of division, which makes replication of DNA essential.

DNA is made up of a double helix of two complementary strands. During replication, these strands are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as semiconservative replication. As a result of semi-conservative replication, the new helix will be composed of an original DNA strand as well as a newly synthesized strand. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication.

In a cell, DNA replication begins at specific locations, or origins of replication, in the genome.

 Unwinding of DNA at the origin and synthesis of new strands, accommodated by an enzyme known as helicase, results in replication forks growing bi-directionally from the origin. A number of proteins are associated with the replication fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by adding nucleotides that complement each (template) strand. DNA replication occurs during the S-stage of interphase.

DNA replication (DNA amplification) can also be performed in vitro (artificially, outside a cell). DNA polymerases isolated from cells and artificial DNA primers can be used to start DNA synthesis at known sequences in a template DNA molecule. Polymerase chain reaction (PCR), ligase chain reaction (LCR), and transcription-mediated amplification (TMA) are examples.

DNA structure

DNA exists as a double-stranded structure, with both strands coiled together to form the characteristic double-helix. Each single strand of DNA is a chain of four types of nucleotides. Nucleotides in DNA contain a deoxyribose sugar, a phosphate, and a nucleobase. The four types of nucleotide correspond to the four nucleobases adenine, cytosine, guanine, and thymine, commonly abbreviated as A, C, G and T. Adenine and guanine are purine bases, while cytosine and thymine are pyrimidines. These nucleotides form phosphodiester bonds, creating the phosphate-deoxyribose backbone of the DNA double helix with the nucleobases pointing inward (i.e., toward the opposing strand). Nucleobases are matched between strands through hydrogen bonds to form base pairs. Adenine pairs with thymine (two hydrogen bonds), and guanine pairs with cytosine (three hydrogen bonds).

DNA strands have a directionality, and the different ends of a single strand are called the "3′ (three-prime) end" and the "5′ (five-prime) end". By convention, if the base sequence of a single strand of DNA is given, the left end of the sequence is the 5′ end, while the right end of the sequence is the 3′ end. The strands of the double helix are anti-parallel with one being 5′ to 3′, and the opposite strand 3′ to 5′. These terms refer to the carbon atom in deoxyribose to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3′ end of a DNA strand.

The pairing of complementary bases in DNA (through hydrogen bonding) means that the information contained within each strand is redundant. Phosphodiester (intra-strand) bonds are stronger than hydrogen (inter-strand) bonds. This allows the strands to be separated from one another. The nucleotides on a single strand can therefore be used to reconstruct nucleotides on a newly synthesized partner strand.

DNA polymerase

DNA polymerases adds nucleotides to the 3′ end of a strand of DNA. If a mismatch is accidentally incorporated, the polymerase is inhibited from further extension. Proofreading removes the mismatched nucleotide and extension continues.

DNA polymerases are a family of enzymes that carry out all forms of DNA replication. DNA polymerases in general cannot initiate synthesis of new strands, but can only extend an existing DNA or RNA strand paired with a template strand. To begin synthesis, a short fragment of RNA, called a primer, must be created and paired with the template DNA strand.

DNA polymerase adds a new strand of DNA by extending the 3′ end of an existing nucleotide chain, adding new nucleotides matched to the template strand one at a time via the creation of phosphodiester bonds. The energy for this process of DNA polymerization comes from hydrolysis of the high-energy phosphate (phosphoanhydride) bonds between the three phosphates attached to each unincorporated base. Free bases with their attached phosphate groups are called nucleotides; in particular, bases with three attached phosphate groups are called nucleoside triphosphates. When a nucleotide is being added to a growing DNA strand, the formation of a phosphodiester bond between the proximal phosphate of the nucleotide to the growing chain is accompanied by hydrolysis of a high-energy phosphate bond with release of the two distal phosphates as a pyrophosphate. Enzymatic hydrolysis of the resulting pyrophosphate into inorganic phosphate consumes a second high-energy phosphate bond and renders the reaction effectively irreversible.

In general, DNA polymerases are highly accurate, with an intrinsic error rate of less than one mistake for every 107 nucleotides added. In addition, some DNA polymerases also have proofreading ability; they can remove nucleotides from the end of a growing strand in order to correct mismatched bases. Finally, post-replication mismatch repair mechanisms monitor the DNA for errors, being capable of distinguishing mismatches in the newly synthesized DNA strand from the original strand sequence. Together, these three discrimination steps enable replication fidelity of less than one mistake for every 109 nucleotides added.

The rate of DNA replication in a living cell was first measured as the rate of phage T4 DNA elongation in phage-infected E. coli. During the period of exponential DNA increase at 37 °C, the rate was 749 nucleotides per second. The mutation rate per base pair per replication during phage T4 DNA synthesis is 1.7 per 108.

Replication process

Overview of the steps in DNA replication
 
Steps in DNA synthesis

DNA replication, like all biological polymerization processes, proceeds in three enzymatically catalyzed and coordinated steps: initiation, elongation and termination.

Initiation

Role of initiators for initiation of DNA replication.
 
Formation of pre-replication complex.

For a cell to divide, it must first replicate its DNA. DNA replication is an all-or-none process; once replication begins, it proceeds to completion. Once replication is complete, it does not occur again in the same cell cycle. This is made possible by the division of initiation of the pre-replication complex.

Pre-replication complex

In late mitosis and early G1 phase, a large complex of initiator proteins assembles into the pre-replication complex at particular points in the DNA, known as "origins". In E. coli the primary initiator protein is DnaA; in yeast, this is the origin recognition complex. Sequences used by initiator proteins tend to be "AT-rich" (rich in adenine and thymine bases), because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair) and thus are easier to strand-separate. In eukaryotes, the origin recognition complex catalyzes the assembly of initiator proteins into the pre-replication complex. Cdc6 and Cdt1 then associate with the bound origin recognition complex at the origin in order to form a larger complex necessary to load the Mcm complex onto the DNA. The Mcm complex is the helicase that will unravel the DNA helix at the replication origins and replication forks in eukaryotes. The Mcm complex is recruited at late G1 phase and loaded by the ORC-Cdc6-Cdt1 complex onto the DNA via ATP-dependent protein remodeling. The loading of the Mcm complex onto the origin DNA marks the completion of pre-replication complex formation.

If environmental conditions are right in late G1 phase, the G1 and G1/S cyclin-Cdk complexes are activated, which stimulate expression of genes that encode components of the DNA synthetic machinery. G1/S-Cdk activation also promotes the expression and activation of S-Cdk complexes, which may play a role in activating replication origins depending on species and cell type. Control of these Cdks vary depending cell type and stage of development.  This regulation is best understood in budding yeast, where the S cyclins Clb5 and Clb6 are primarily responsible for DNA replication. Clb5,6-Cdk1 complexes directly trigger the activation of replication origins and are therefore required throughout S phase to directly activate each origin.

In a similar manner, Cdc7 is also required through S phase to activate replication origins. Cdc7 is not active throughout the cell cycle, and its activation is strictly timed to avoid premature initiation of DNA replication. In late G1, Cdc7 activity rises abruptly as a result of association with the regulatory subunit Dbf4, which binds Cdc7 directly and promotes its protein kinase activity. Cdc7 has been found to be a rate-limiting regulator of origin activity. Together, the G1/S-Cdks and/or S-Cdks and Cdc7 collaborate to directly activate the replication origins, leading to initiation of DNA synthesis.

Preinitiation complex

In early S phase, S-Cdk and Cdc7 activation lead to the assembly of the preinitiation complex, a massive protein complex formed at the origin. Formation of the preinitiation complex displaces Cdc6 and Cdt1 from the origin replication complex, inactivating and disassembling the pre-replication complex. Loading the preinitiation complex onto the origin activates the Mcm helicase, causing unwinding of the DNA helix.  The preinitiation complex also loads α-primase and other DNA polymerases onto the DNA.

After α-primase synthesizes the first primers, the primer-template junctions interact with the clamp loader, which loads the sliding clamp onto the DNA to begin DNA synthesis. The components of the preinitiation complex remain associated with replication forks as they move out from the origin.

Elongation

DNA polymerase has 5′–3′ activity. All known DNA replication systems require a free 3′ hydroxyl group before synthesis can be initiated (note: the DNA template is read in 3′ to 5′ direction whereas a new strand is synthesized in the 5′ to 3′ direction—this is often confused). Four distinct mechanisms for DNA synthesis are recognized:

  1. All cellular life forms and many DNA viruses, phages and plasmids use a primase to synthesize a short RNA primer with a free 3′ OH group which is subsequently elongated by a DNA polymerase.
  2. The retroelements (including retroviruses) employ a transfer RNA that primes DNA replication by providing a free 3′ OH that is used for elongation by the reverse transcriptase.
  3. In the adenoviruses and the φ29 family of bacteriophages, the 3′ OH group is provided by the side chain of an amino acid of the genome attached protein (the terminal protein) to which nucleotides are added by the DNA polymerase to form a new strand.
  4. In the single stranded DNA viruses—a group that includes the circoviruses, the geminiviruses, the parvoviruses and others—and also the many phages and plasmids that use the rolling circle replication (RCR) mechanism, the RCR endonuclease creates a nick in the genome strand (single stranded viruses) or one of the DNA strands (plasmids). The 5′ end of the nicked strand is transferred to a tyrosine residue on the nuclease and the free 3′ OH group is then used by the DNA polymerase to synthesize the new strand.

The first is the best known of these mechanisms and is used by the cellular organisms. In this mechanism, once the two strands are separated, primase adds RNA primers to the template strands. The leading strand receives one RNA primer while the lagging strand receives several. The leading strand is continuously extended from the primer by a DNA polymerase with high processivity, while the lagging strand is extended discontinuously from each primer forming Okazaki fragments. RNase removes the primer RNA fragments, and a low processivity DNA polymerase distinct from the replicative polymerase enters to fill the gaps. When this is complete, a single nick on the leading strand and several nicks on the lagging strand can be found. Ligase works to fill these nicks in, thus completing the newly replicated DNA molecule.

The primase used in this process differs significantly between bacteria and archaea/eukaryotes. Bacteria use a primase belonging to the DnaG protein superfamily which contains a catalytic domain of the TOPRIM fold type. The TOPRIM fold contains an α/β core with four conserved strands in a Rossmann-like topology. This structure is also found in the catalytic domains of topoisomerase Ia, topoisomerase II, the OLD-family nucleases and DNA repair proteins related to the RecR protein.

The primase used by archaea and eukaryotes, in contrast, contains a highly derived version of the RNA recognition motif (RRM). This primase is structurally similar to many viral RNA-dependent RNA polymerases, reverse transcriptases, cyclic nucleotide generating cyclases and DNA polymerases of the A/B/Y families that are involved in DNA replication and repair. In eukaryotic replication, the primase forms a complex with Pol α.

Multiple DNA polymerases take on different roles in the DNA replication process. In E. coli, DNA Pol III is the polymerase enzyme primarily responsible for DNA replication. It assembles into a replication complex at the replication fork that exhibits extremely high processivity, remaining intact for the entire replication cycle. In contrast, DNA Pol I is the enzyme responsible for replacing RNA primers with DNA. DNA Pol I has a 5′ to 3′ exonuclease activity in addition to its polymerase activity, and uses its exonuclease activity to degrade the RNA primers ahead of it as it extends the DNA strand behind it, in a process called nick translation. Pol I is much less processive than Pol III because its primary function in DNA replication is to create many short DNA regions rather than a few very long regions.

In eukaryotes, the low-processivity enzyme, Pol α, helps to initiate replication because it forms a complex with primase. In eukaryotes, leading strand synthesis is thought to be conducted by Pol ε; however, this view has recently been challenged, suggesting a role for Pol δ. Primer removal is completed Pol δ while repair of DNA during replication is completed by Pol ε.

As DNA synthesis continues, the original DNA strands continue to unwind on each side of the bubble, forming a replication fork with two prongs. In bacteria, which have a single origin of replication on their circular chromosome, this process creates a "theta structure" (resembling the Greek letter theta: θ). In contrast, eukaryotes have longer linear chromosomes and initiate replication at multiple origins within these.

Replication fork

Scheme of the replication fork.
a: template, b: leading strand, c: lagging strand, d: replication fork, e: primer, f: Okazaki fragments
 
Many enzymes are involved in the DNA replication fork.

The replication fork is a structure that forms within the long helical DNA during DNA replication. It is created by helicases, which break the hydrogen bonds holding the two DNA strands together in the helix. The resulting structure has two branching "prongs", each one made up of a single strand of DNA. These two strands serve as the template for the leading and lagging strands, which will be created as DNA polymerase matches complementary nucleotides to the templates; the templates may be properly referred to as the leading strand template and the lagging strand template.

DNA is read by DNA polymerase in the 3′ to 5′ direction, meaning the nascent strand is synthesized in the 5' to 3' direction. Since the leading and lagging strand templates are oriented in opposite directions at the replication fork, a major issue is how to achieve synthesis of nascent (new) lagging strand DNA, whose direction of synthesis is opposite to the direction of the growing replication fork.

Leading strand

The leading strand is the strand of nascent DNA which is synthesized in the same direction as the growing replication fork. This sort of DNA replication is continuous.

Lagging strand

The lagging strand is the strand of nascent DNA whose direction of synthesis is opposite to the direction of the growing replication fork. Because of its orientation, replication of the lagging strand is more complicated as compared to that of the leading strand. As a consequence, the DNA polymerase on this strand is seen to "lag behind" the other strand.

The lagging strand is synthesized in short, separated segments. On the lagging strand template, a primase "reads" the template DNA and initiates synthesis of a short complementary RNA primer. A DNA polymerase extends the primed segments, forming Okazaki fragments. The RNA primers are then removed and replaced with DNA, and the fragments of DNA are joined together by DNA ligase.

Dynamics at the replication fork

The assembled human DNA clamp, a trimer of the protein PCNA.

In all cases the helicase is composed of six polypeptides that wrap around only one strand of the DNA being replicated. The two polymerases are bound to the helicase heximer. In eukaryotes the helicase wraps around the leading strand, and in prokaryotes it wraps around the lagging strand.

As helicase unwinds DNA at the replication fork, the DNA ahead is forced to rotate. This process results in a build-up of twists in the DNA ahead. This build-up forms a torsional resistance that would eventually halt the progress of the replication fork. Topoisomerases are enzymes that temporarily break the strands of DNA, relieving the tension caused by unwinding the two strands of the DNA helix; topoisomerases (including DNA gyrase) achieve this by adding negative supercoils to the DNA helix.

Bare single-stranded DNA tends to fold back on itself forming secondary structures; these structures can interfere with the movement of DNA polymerase. To prevent this, single-strand binding proteins bind to the DNA until a second strand is synthesized, preventing secondary structure formation.

Double-stranded DNA is coiled around histones that play an important role in regulating gene expression so the replicated DNA must be coiled around histones at the same places as the original DNA. To ensure this, histone chaperones disassemble the chromatin before it is replicated and replace the histones in the correct place. Some steps in this reassembly are somewhat speculative.

Clamp proteins form a sliding clamp around DNA, helping the DNA polymerase maintain contact with its template, thereby assisting with processivity. The inner face of the clamp enables DNA to be threaded through it. Once the polymerase reaches the end of the template or detects double-stranded DNA, the sliding clamp undergoes a conformational change that releases the DNA polymerase. Clamp-loading proteins are used to initially load the clamp, recognizing the junction between template and RNA primers.

DNA replication proteins

At the replication fork, many replication enzymes assemble on the DNA into a complex molecular machine called the replisome. The following is a list of major DNA replication enzymes that participate in the replisome:

Enzyme Function in DNA replication
DNA helicase Also known as helix destabilizing enzyme. Helicase separates the two strands of DNA at the Replication Fork behind the topoisomerase.
DNA polymerase The enzyme responsible for catalyzing the addition of nucleotide substrates to DNA in the 5′ to 3′ direction during DNA replication. Also performs proof-reading and error correction. There exist many different types of DNA Polymerase, each of which perform different functions in different types of cells.
DNA clamp A protein which prevents elongating DNA polymerases from dissociating from the DNA parent strand.
Single-strand DNA-binding protein Bind to ssDNA and prevent the DNA double helix from re-annealing after DNA helicase unwinds it, thus maintaining the strand separation, and facilitating the synthesis of the nascent strand.
Topoisomerase Relaxes the DNA from its super-coiled nature.
DNA gyrase Relieves strain of unwinding by DNA helicase; this is a specific type of topoisomerase
DNA ligase Re-anneals the semi-conservative strands and joins Okazaki Fragments of the lagging strand.
Primase Provides a starting point of RNA (or DNA) for DNA polymerase to begin synthesis of the new DNA strand.
Telomerase Lengthens telomeric DNA by adding repetitive nucleotide sequences to the ends of eukaryotic chromosomes. This allows germ cells and stem cells to avoid the Hayflick limit on cell division.[29]

Replication machinery

E. coli Replisome. Notably, the DNA on lagging strand forms a loop. The exact structure of replisome is not well understood.

Replication machineries consist of factors involved in DNA replication and appearing on template ssDNAs. Replication machineries include primosotors are replication enzymes; DNA polymerase, DNA helicases, DNA clamps and DNA topoisomerases, and replication proteins; e.g. single-stranded DNA binding proteins (SSB). In the replication machineries these components coordinate. In most of the bacteria, all of the factors involved in DNA replication are located on replication forks and the complexes stay on the forks during DNA replication. These replication machineries are called replisomes or DNA replicase systems. These terms are generic terms for proteins located on replication forks. In eukaryotic and some bacterial cells the replisomes are not formed.

Since replication machineries do not move relatively to template DNAs such as factories, they are called a replication factory. In an alternative figure, DNA factories are similar to projectors and DNAs are like as cinematic films passing constantly into the projectors. In the replication factory model, after both DNA helicases for leading strands and lagging strands are loaded on the template DNAs, the helicases run along the DNAs into each other. The helicases remain associated for the remainder of replication process. Peter Meister et al. observed directly replication sites in budding yeast by monitoring green fluorescent protein (GFP)-tagged DNA polymerases α. They detected DNA replication of pairs of the tagged loci spaced apart symmetrically from a replication origin and found that the distance between the pairs decreased markedly by time. This finding suggests that the mechanism of DNA replication goes with DNA factories. That is, couples of replication factories are loaded on replication origins and the factories associated with each other. Also, template DNAs move into the factories, which bring extrusion of the template ssDNAs and nascent DNAs. Meister's finding is the first direct evidence of replication factory model. Subsequent research has shown that DNA helicases form dimers in many eukaryotic cells and bacterial replication machineries stay in single intranuclear location during DNA synthesis.

The replication factories perform disentanglement of sister chromatids. The disentanglement is essential for distributing the chromatids into daughter cells after DNA replication. Because sister chromatids after DNA replication hold each other by Cohesin rings, there is the only chance for the disentanglement in DNA replication. Fixing of replication machineries as replication factories can improve the success rate of DNA replication. If replication forks move freely in chromosomes, catenation of nuclei is aggravated and impedes mitotic segregation.

Termination

Eukaryotes initiate DNA replication at multiple points in the chromosome, so replication forks meet and terminate at many points in the chromosome. Because eukaryotes have linear chromosomes, DNA replication is unable to reach the very end of the chromosomes. Due to this problem, DNA is lost in each replication cycle from the end of the chromosome. Telomeres are regions of repetitive DNA close to the ends and help prevent loss of genes due to this shortening. Shortening of the telomeres is a normal process in somatic cells. This shortens the telomeres of the daughter DNA chromosome. As a result, cells can only divide a certain number of times before the DNA loss prevents further division. (This is known as the Hayflick limit.) Within the germ cell line, which passes DNA to the next generation, telomerase extends the repetitive sequences of the telomere region to prevent degradation. Telomerase can become mistakenly active in somatic cells, sometimes leading to cancer formation. Increased telomerase activity is one of the hallmarks of cancer.

Termination requires that the progress of the DNA replication fork must stop or be blocked. Termination at a specific locus, when it occurs, involves the interaction between two components: (1) a termination site sequence in the DNA, and (2) a protein which binds to this sequence to physically stop DNA replication. In various bacterial species, this is named the DNA replication terminus site-binding protein, or Ter protein.

Because bacteria have circular chromosomes, termination of replication occurs when the two replication forks meet each other on the opposite end of the parental chromosome. E. coli regulates this process through the use of termination sequences that, when bound by the Tus protein, enable only one direction of replication fork to pass through. As a result, the replication forks are constrained to always meet within the termination region of the chromosome.

Regulation

The cell cycle of eukaryotic cells.

Eukaryotes

Within eukaryotes, DNA replication is controlled within the context of the cell cycle. As the cell grows and divides, it progresses through stages in the cell cycle; DNA replication takes place during the S phase (synthesis phase). The progress of the eukaryotic cell through the cycle is controlled by cell cycle checkpoints. Progression through checkpoints is controlled through complex interactions between various proteins, including cyclins and cyclin-dependent kinases. Unlike bacteria, eukaryotic DNA replicates in the confines of the nucleus.

The G1/S checkpoint (or restriction checkpoint) regulates whether eukaryotic cells enter the process of DNA replication and subsequent division. Cells that do not proceed through this checkpoint remain in the G0 stage and do not replicate their DNA.

After passing through the G1/S checkpoint, DNA must be replicated only once in each cell cycle. When the Mcm complex moves away from the origin, the pre-replication complex is dismantled. Because a new Mcm complex cannot be loaded at an origin until the pre-replication subunits are reactivated, one origin of replication can not be used twice in the same cell cycle.

Activation of S-Cdks in early S phase promotes the destruction or inhibition of individual pre-replication complex components, preventing immediate reassembly. S and M-Cdks continue to block pre-replication complex assembly even after S phase is complete, ensuring that assembly cannot occur again until all Cdk activity is reduced in late mitosis.

In budding yeast, inhibition of assembly is caused by Cdk-dependent phosphorylation of pre-replication complex components. At the onset of S phase, phosphorylation of Cdc6 by Cdk1 causes the binding of Cdc6 to the SCF ubiquitin protein ligase, which causes proteolytic destruction of Cdc6. Cdk-dependent phosphorylation of Mcm proteins promotes their export out of the nucleus along with Cdt1 during S phase, preventing the loading of new Mcm complexes at origins during a single cell cycle. Cdk phosphorylation of the origin replication complex also inhibits pre-replication complex assembly. The individual presence of any of these three mechanisms is sufficient to inhibit pre-replication complex assembly. However, mutations of all three proteins in the same cell does trigger reinitiation at many origins of replication within one cell cycle.

In animal cells, the protein geminin is a key inhibitor of pre-replication complex assembly. Geminin binds Cdt1, preventing its binding to the origin recognition complex. In G1, levels of geminin are kept low by the APC, which ubiquitinates geminin to target it for degradation. When geminin is destroyed, Cdt1 is released, allowing it to function in pre-replication complex assembly. At the end of G1, the APC is inactivated, allowing geminin to accumulate and bind Cdt1.

Replication of chloroplast and mitochondrial genomes occurs independently of the cell cycle, through the process of D-loop replication.

Replication focus

In vertebrate cells, replication sites concentrate into positions called replication foci. Replication sites can be detected by immunostaining daughter strands and replication enzymes and monitoring GFP-tagged replication factors. By these methods it is found that replication foci of varying size and positions appear in S phase of cell division and their number per nucleus is far smaller than the number of genomic replication forks.

P. Heun et al.,(2001) tracked GFP-tagged replication foci in budding yeast cells and revealed that replication origins move constantly in G1 and S phase and the dynamics decreased significantly in S phase. Traditionally, replication sites were fixed on spatial structure of chromosomes by nuclear matrix or lamins. The Heun's results denied the traditional concepts, budding yeasts do not have lamins, and support that replication origins self-assemble and form replication foci.

By firing of replication origins, controlled spatially and temporally, the formation of replication foci is regulated. D. A. Jackson et al.(1998) revealed that neighboring origins fire simultaneously in mammalian cells. Spatial juxtaposition of replication sites brings clustering of replication forks. The clustering do rescue of stalled replication forks and favors normal progress of replication forks. Progress of replication forks is inhibited by many factors; collision with proteins or with complexes binding strongly on DNA, deficiency of dNTPs, nicks on template DNAs and so on. If replication forks stall and the remaining sequences from the stalled forks are not replicated, the daughter strands have nick obtained un-replicated sites. The un-replicated sites on one parent's strand hold the other strand together but not daughter strands. Therefore, the resulting sister chromatids cannot separate from each other and cannot divide into 2 daughter cells. When neighboring origins fire and a fork from one origin is stalled, fork from other origin access on an opposite direction of the stalled fork and duplicate the un-replicated sites. As other mechanism of the rescue there is application of dormant replication origins that excess origins do not fire in normal DNA replication.

Bacteria

Dam methylates adenine of GATC sites after replication.

Most bacteria do not go through a well-defined cell cycle but instead continuously copy their DNA; during rapid growth, this can result in the concurrent occurrence of multiple rounds of replication. In E. coli, the best-characterized bacteria, DNA replication is regulated through several mechanisms, including: the hemimethylation and sequestering of the origin sequence, the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and the levels of protein DnaA. All these control the binding of initiator proteins to the origin sequences.

Because E. coli methylates GATC DNA sequences, DNA synthesis results in hemimethylated sequences. This hemimethylated DNA is recognized by the protein SeqA, which binds and sequesters the origin sequence; in addition, DnaA (required for initiation of replication) binds less well to hemimethylated DNA. As a result, newly replicated origins are prevented from immediately initiating another round of DNA replication.

ATP builds up when the cell is in a rich medium, triggering DNA replication once the cell has reached a specific size. ATP competes with ADP to bind to DnaA, and the DnaA-ATP complex is able to initiate replication. A certain number of DnaA proteins are also required for DNA replication — each time the origin is copied, the number of binding sites for DnaA doubles, requiring the synthesis of more DnaA to enable another initiation of replication.

In fast-growing bacteria, such as E. coli, chromosome replication takes more time than dividing the cell. The bacteria solve this by initiating a new round of replication before the previous one has been terminated. The new round of replication will form the chromosome of the cell that is born two generations after the dividing cell. This mechanism creates overlapping replication cycles.

Problems with DNA replication

Replication fork restarts by homologous recombination following replication stress
 
Epigenetic consequences of nucleosome reassembly defects at stalled replication forks

There are many events that contribute to replication stress, including:

Polymerase chain reaction

Researchers commonly replicate DNA in vitro using the polymerase chain reaction (PCR). PCR uses a pair of primers to span a target region in template DNA, and then polymerizes partner strands in each direction from these primers using a thermostable DNA polymerase. Repeating this process through multiple cycles amplifies the targeted DNA region. At the start of each cycle, the mixture of template and primers is heated, separating the newly synthesized molecule and template. Then, as the mixture cools, both of these become templates for annealing of new primers, and the polymerase extends from these. As a result, the number of copies of the target region doubles each round, increasing exponentially.

 

Introduction to entropy

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